J Rheum Dis.  2015 Aug;22(4):242-245. 10.4078/jrd.2015.22.4.242.

A Case of Azathioprine Induced Warfarin Resistance in Behcet's Disease

• Kim SR
• Leem DW
• Moon IJ
• Koh BS
• Chang MH
• Yoo J
• Yang HC
• Lee CH

• KMID: 2222855
• DOI: http://doi.org/10.4078/jrd.2015.22.4.242

Abstract

Behcet's disease is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Thrombosis associated with vascular inflammation in patients with Behcet's disease presents various clinical symptoms. Warfarin is usually administered for treatment of thrombosis. However, warfarin can interact with many medications that cause various problems. A 43-year-old woman with Behcet's disease presented with a swollen right leg. Deep vein thrombosis (DVT) was confirmed, and treated with warfarin. Due to exacerbation of Behcet's disease, she received azathioprine along with warfarin. Subsequently, the international normalized ratio (INR) decreased and DVT was exacerbated. Despite an increase in the warfarin dose, the patient did not reach the target INR. After discontinuation of azathioprine, DVT improved and the warfarin dose was decreased. There were no specific findings associated with a hypercoagulable status. This finding suggests the interaction of azathioprine and warfarin. Therefore, clinicians should be cautious regarding the possibility of drug interactions between azathioprine and warfarin.

Keyword

Behcet's disease; Azathioprine; Warfarin; Drug interactions

MeSH Terms

Adult
Azathioprine*
Drug Interactions
Female
Humans
Inflammation
International Normalized Ratio
Leg
Skin
Stomatitis, Aphthous
Thrombosis
Ulcer
Uveitis
Venous Thrombosis
Warfarin*
Azathioprine
Warfarin

Figure

• 

  Figure 1. Computed tomography showing deep vein thrombosis (DVT) at the right deep femoral vein (black arrow) and the right superficial femoral vein (white arrow) in June 2012, and the persistence and worsening of those DVTs in January 2013.

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  Figure 2. Patient international normalized ratio (INR) according to the warfarin and azathioprine dose. INR decreased to below 2 with 2 mg warfarin treatment, after azathioprine initiation (thin arrow). Nevertheless, when the warfarin dose was increased to 5 mg, the INR was consistently below 2. Upon deep vein thrombosis recurrence (January 7, 2013), the warfarin dose was increased to 10 mg, after which the INR increased to 3.59. Therefore, the warfarin dose was decreased to 7 mg. During treatment with 7 mg warfarin for a month, the INR decreased to 2.13 (thin double-headed arrow). To rule out the possibility of an interaction between azathioprine and warfarin, we discontinued azathioprine (thick arrow). Subsequently, the INR increased to 4.15 during treatment with 7 mg warfarin for a month (thick double-headed arrow), unlike the reaction previously noted. Thereafter, the warfarin dose could be reduced to 4 mg to sustain the constant INR.

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  Figure 3. Computed tomography showing a newly developed right posterior tibial vein thrombosis (black arrow) in January 2013, which was undetectable in June 2012.

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